HER2-positive breast cancer are known for there high levels in protein human epidermal growth factor receptor 2. This kind of cancer are known to grow and spreads more rapidly than that of the HER2-negative breast cancer, but they are not nearly as common.

HER2 proteins in breast cancer

If you have a loved one or a friend who has received a breast cancer diagnosis, you would have probably heard the term called HER2. You may be wondering what it means to have HER2-negative or HER2-positive breast cancer.

HER2 stands for human epidermal growth factor receptor 2. The HER2 protein was discovered in the 1980s.

HER2 proteins are found on the surface of breast cells. They’re involved in normal cell growth but can become overexpressed. This means that a person’s levels of the protein are higher than usual.

In the 1980s, researchers determined that too many HER2 proteins could cause cancer to grow and spread more quickly. This discovery led to research on how to slow or alter the growth of HER2-positive breast cancer cells.

What HER2-negative means

If breast cancer cells do not have abnormal levels of HER2 proteins, the breast cancer is considered HER2-negative.

Even if your cancer is HER2-negative, it may still be estrogen-positive or progesterone-positive. Whether or not it’s hormone-positive also affects your treatment options.

In the United States, HER2-negative cases accounted for 78% of new female breast cancer cases between 2015 and 2019, according to the National Cancer Institute (NCI). In 7% of cases, the HER2 status was unknown.

HER2-negative breast cancer HER2-positive breast cancer
does not have abnormal levels of HER2 proteins has abnormally high levels of HER2 proteins, causing the cancer to grow and spread more quickly
accounted for 78% of new female breast cancer cases in the United States between 2015 and 2019 accounted for 14% of new female breast cancer cases in the United States between 2015 and 2019
can be hormone-positive or hormone-negative can be hormone-positive or hormone-negative
less likely to be treated with targeted therapies primarily treated with the targeted therapy trastuzumab (Herceptin), but may also be treated with one or more other targeted therapies, including pertuzumab (Perjeta)
may also be treated with chemotherapy may also be treated with chemotherapy

What HER2-positive means

HER2-positive breast cancers have abnormally high levels of HER2 proteins.

This can cause the cells to multiply more quickly. Excessive reproduction can result in a fast-growing breast cancer that’s more likely to spread.

HER2-positive cases accounted for 14% of new female breast cancer cases in the United States between 2015 and 2019.

In the last 3 decades, significant progress has been made regarding treatment options for HER2-positive breast cancer.

HER2-low breast cancer

HER2-low breast cancer is a new classification that’s used to describe cancer where HER2 proteins are present, but there aren’t enough for the cancer to be considered HER2-positive. These cancers have traditionally been classified as HER2-negative.

Around 50% to 60% of breast cancers are actually HER2-low breast cancers, according to the National Cancer Institute (NCI).

Treatment may include the targeted therapy fam-trastuzumab deruxtecan (Enhertu).

Testing for HER2

It’s important for a doctor to test for overexpression of HER2 because the results will determine whether you’ll benefit from certain medications.

Tests that can determine HER2 status include:

  • in situ hybridization (ISH) tests, such as the fluorescence in situ hybridization (FISH) test
  • immunohistochemistry (IHC) test

For both tests, you’ll provide a tissue sample.

An ISH test is a type of genetic test. During this test, a pathologist examines your DNA to see if you have too many copies of the HER2 gene. In an IHC test, a pathologist actually counts the number of HER2 proteins on the breast cancer cells.

The Food and Drug Administration (FDA) has approved several types of ISH and IHC tests.

ISH tests are not as widely available as IHC tests, but they’re more accurate.

How HER2 affects staging

As of 2018, the breast cancer staging system that the American Joint Committee on Cancer developed now incorporates HER2 status.

Your HER2 status can help determine how aggressive your cancer is. Your doctor will use this information to evaluate your treatment options.

Staging is complex and must take various other factors into account as well, such as:

  • the size of the tumors
  • the cancer’s hormone status
  • whether the cancer has spread to nearby lymph nodes
  • whether the cancer has spread beyond the breast
  • whether the cancer cells look unusual

For example, these two cancers are both classified as stage 1B:

HER2-negative breast cancer (stage 1B) HER2-positive breast cancer (stage 1B)
tumors between 2 and 5 centimeters (cm) tumors between 2 and 5 cm
hormone-positive estrogen-positive and progesterone-positive
has not spread to the lymph nodes or away from the breast has spread to 1 of 3 axillary (armpit) lymph nodes

Speak with your doctor if you’d like to learn more about your cancer stage.

How HER2 status affects treatment

For more than 30 years, researchers have been studying HER2-positive breast cancer and ways to treat it.

Targeted therapies have now changed the outlook for people with stage 1, 2, and 3 breast cancers from poor to good.

While targeted therapies are part of the standard treatment for HER2-positive breast cancer, they’re used less often in HER2-negative breast cancer.

In general, your breast cancer treatment regimen will depend on your cancer’s:

  • HER2 status
  • hormone receptor status
  • stage

For HER2-positive or HER2-negative breast cancers that are estrogen-positive or progesterone-positive, treatment with hormone therapy may also be recommended.

Some people may also receive chemotherapy, depending on their cancer stage.

Other factors that may affect your breast cancer treatment regimen include whether:

  • you’ve already received hormone therapy or chemotherapy
  • you’ve gone through menopause
  • you have gene mutations other than HER2

Treatments for HER2-negative breast cancer

Medications that may be used to treat HER2-negative breast cancers that are hormone-negative include:

  • pembrolizumab (Keytruda)
  • sacituzumab govitecan (Trodelvy)
  • talazoparib (Talzenna)

Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:

  • abemaciclib (Verzenio)
  • alpelisib (Piqray)
  • everolimus (Afinitor)
  • olaparib (Lynparza)
  • palbociclib (Ibrance)
  • ribociclib (Kisqali)

Most of the medications in the previous list are taken in combination with some form of hormone treatment.

Treatments for HER2-positive breast cancer

Trastuzumab (Herceptin), when used in tandem with chemotherapy, has improved the outlook of those with HER2-positive breast cancer. This targeted drug is often the primary treatment for the condition.

Trastuzumab (Herceptin) is a biologic therapy that’s administered intravenously.

A 2018 literature review showed that the use of trastuzumab with chemotherapy slowed the growth of HER2-positive breast cancer better than chemotherapy alone. For some, this combination has resulted in long lasting periods of remission.

Curative treatment with this medication lasts for up to 52 weeks. If you have metastatic or recurrent cancer, you may take it for much longer. Cardiac monitoring will continue for at least 2 years after treatment ends, due to the risk of side effects.

Other treatments for HER2-positive breast cancer include but are not limited to these targeted therapies:

  • Herceptin biosimilars: Biosimilars are not exact copies of biologic drugs, but they’re reverse-engineered to produce similar effects. The FDA has approved five Herceptin biosimilars, including trastuzumab-dkst (Ogivri) and trastuzumab-qyyp (Trazimera).
  • Trastuzumab/hyaluronidase-oysk (Herceptin Hylecta): The FDA approved Herceptin Hylecta in 2019. Herceptin Hylecta is an injectable medication. As a result, it can be administered more quickly than Herceptin. Cardiac monitoring is also required.
  • Pertuzumab (Perjeta): In some cases, pertuzumab (Perjeta) may be used in conjunction with Herceptin. This may be recommended for HER2-positive breast cancers at a higher risk of recurrence, like stage 2 and above, or for cancers that have spread to the lymph nodes.
  • Neratinib (Nerlynx): Neratinib (Nerlynx) may be recommended after treatment with Herceptin in cases that have a higher risk of recurrence.
  • Margetuximab-cmkb (Margenza): This is one of the newest HER2 medications. It’s used to treat more advanced or metastatic breast cancer in people who have received at least two previous HER2 treatments.
  • Fam-trastuzumab deruxtecan (Enhertu): This versatile medication is used as a second- or third-line treatment for non-small cell lung cancer, advanced stomach cancer, and some cases of HER2-positive breast cancer. This includes cases where the breast cancer cannot be removed with surgery or it’s metastatic. In August 2022, the FDA also approved its use in some cases of HER2-low metastatic breast cancer.

Takeaway

If you’ve received a diagnosis of invasive breast cancer, a doctor will test your cancer to determine its HER2 status. The test results will help inform which treatment options are best for your cancer.

New developments in the treatment of HER2-positive breast cancer have improved the outlook for people with this fast-growing type of cancer. Research is underway for new treatments, and survival rates for people with breast cancer are improving all the time.

If you receive a diagnosis of HER2-positive breast cancer, do not hesitate to talk openly with a doctor about your cancer and ask any questions that you may have.

Frequently Asked Questions

Listen to pronunciation. (… NEH-guh-tiv) Describes cells that have a small amount or none of a protein called HER2 on their surface.
Conclusions: The triple negative subtype has the worst survival regardless of stage. HER2-positive cancers are heterogeneous and not all have poor survival. ER and PR must be considered. ER status appears to influence 5-year survival more than HER2 status.
A positive test for HER2 means breast cancer may grow quickly and possibly come back (recur). This risk is significantly lowered with appropriate treatment. At the Abramson Cancer Center, we treat HER2-positive breast cancer with medications that work to slow or stop tumor growth.
Many women with hormone-positive, HER2-negative, lymph node-negative early-stage breast cancer who have intermediate risk of cancer recurrence do not need chemotherapy. The exception is that some women who are younger than 50 may benefit when chemotherapy is added to hormone therapy.
Treatments for HER2-Negative Breast Cancer. The options for treating HER2-negative breast cancer include: Surgery and/or radiation. If your HER2-negative cancer is caught early, a surgeon may be able to remove it completely. Your doctor might also recommend radiation before or after surgery.
Hormonal therapy is considered the standard initial treatment for HER2-negative metastatic breast cancer that is also hormone receptor-positive. It is often given in combination with targeted therapy. However, chemotherapy may also be given. A clinical trial may also be an option for treatment at any stage.
The treatment of HER2-positive breast cancer will depend on your preferences as well as the characteristics of your cancer: Many women with HER2-positive breast cancer will get neoadjuvant chemotherapy first, along with medication that targets HER2 directly (see ‘Chemotherapy’ below and ‘HER2-directed therapy’ below).
For HER2-positive tumors, the targeted drug trastuzumab is given as well, often along with pertuzumab (Perjeta). This may shrink the tumor enough for a woman to have breast-conserving surgery (BCS). If the tumor doesn’t shrink enough, a mastectomy is done. Nearby lymph nodes will also need to be checked.
Because HER2-positive cancer is considered more aggressive than HER2-negative breast cancer, it is usually treated with chemotherapy after surgery to reduce recurrence risk.
HER2-positive breast cancer is more aggressive and more likely to recur, or return, than HER2-negative breast cancer. Recurrence can happen anytime, but it usually takes place within 5 years of treatment. The good news is that recurrence is less likely now than ever before.
Your HER2 status can change as your cancer grows or returns. That is, HER2-positive cancer can become HER2-negative and vice versa. You and your doctor may decide to retest for HER2 over time or if your cancer comes back after treatment.
As with all types of breast cancer, what exactly causes HER2-positive breast cancer is unknown. It’s likely a combination of risk factors, including lifestyle and environment. Genetics are also thought to play a role. However, the HER2 gene is not inherited from parents and can’t be passed on to children.
Conclusion. Based on our case, although rare, patients with treated, operable, hormone receptor positive, HER2 negative breast cancer can present with solitary brain metastasis as the only sign of disease recurrence.
Most breast cancers are HER2-negative. According to the National Cancer Institute (NCI), an estimated 78 percent of breast cancers are HER2-negative and don’t produce too much HER2.
In about 1 of every 5 breast cancers, the cancer cells have extra copies of the gene that makes the HER2 protein. HER2 -positive breast cancers tend to be more aggressive than other types of breast cancer.
Since this protein can make cancer cells grow more quickly, it’s natural to worry that your HER2-positive breast cancer might spread, or “metastasize.” If breast cancer spreads to other parts of your body, doctors call it “metastatic.” That means it’s at a more advanced stage than if it’s only in your breasts.
Hormone receptor-positive cancers tend to grow more slowly than those that are hormone receptor-negative. Women with hormone receptor-positive cancers tend to have a better outlook in the short-term, but these cancers can sometimes come back many years after treatment.
HER2-positive breast cancer is a highly heterogeneous tumor, and about 30% of patients still suffer from recurrence and metastasis after trastuzumab targeted therapy.

If your breast cancer has spread to your lymph nodes, your doctor may recommend chemotherapy. Age. Breast cancer that occurs at a younger age may be more aggressive than cancer that develops later in life. So doctors may recommend that younger people with breast cancer undergo chemotherapy.
If a tumor is HER2-positive, the HER2-targeted therapy drug trastuzumab (Herceptin) is included in the chemotherapy regimen. Sometimes other drugs that target HER2 are used. Pertuzumab (Perjeta) can be combined with trastuzumab, and neratinib (Nerlynx) can be given after trastuzumab.
Invasive ductal carcinoma (IDC) can be described as a stage 1 (earliest stage) to a stage IV (most advanced stage), depending on the size of the tumor and how far it has spread. Learn more about the stages of breast cancer.
Black pepper contains an active compound called piperine. Piperine has an anti-tumor effect on HER2-positive breast cancer cells. This means that it stops the cells from growing and causes them to die. Piperine was also found to stop the HER2 gene from making HER2 proteins.
During a course of treatment, you usually have around 4 to 8 cycles of treatment. A cycle is the time between one round of treatment until the start of the next. After each round of treatment you have a break, to allow your body to recover.
HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status.
HER2-positive breast cancer is not inherited. Instead, it’s considered a somatic genetic mutation. This type of mutation occurs after conception. Having a close relative with HER2-positive breast cancer does not increase your risk for breast cancer or HER2-positive breast cancer.